Panitumumab, gemcitabine, and irinotecan in patients with advanced or metastatic cholangiocarcinoma: A phase II study.

Abstract

TPS214 Background: Cholangiocarcinoma is an aggressive neoplasm with rising incidence. Cytotoxic chemotherapy agents have moderate effects either as single agents or combinations. More effective treatments are needed, especially treatments based on molecular cancer characteristics. Overexpression of epidermal growth factor receptor (EGFR) is associated with tumor stage, lymph node metastasis, lymphovascular and perineural invasion of cholangiocarcinoma, and is an independent indicator of poor prognosis (Yoshikawa D, et al. Br J Cancer 2008 98:418-25). A phase II study showed some activity with erlotinib as single agent (Philip P, et al. JCO 2006 24:3069-74); moreover, a small trial suggested that cetuximab may circumvent tumor resistance to chemotherapy (Paule B, et al. Oncology 2007;72:105-10). This ongoing phase II study is designed to evaluate the efficacy and tolerability of adding panitumumab, a monoclonal anti-EGFR antibody, to combined gemcitabine and irinotecan that we previously developed in this disease (Sun W, et al. Cancer 2007 110:2768-74) in patients with advanced and metastatic cholangiocarcinoma. Methods: Patients with advanced unresectable or metastatic cholangiocarcinoma, ECOG PS 0-2, adequate liver, kidney and bone marrow function were treated with panitumumab (9 mg/kg) on day 1, gemcitabine (1000 mg/m2/100 min) iv and irinotecan (100 mg/m2) iv on days 1 and 8 of a 21-day cycle. Tissue specimens were collected based on availability for future biomarker analyses. The primary objective is to evaluate the 5-month progression-free survival (PFS) rate. A true 5-month PFS rate of 65% or more will be taken as evidence of activity in this patient population. Response rate, overall survival rate and tolerability/feasibility are tested also. No significant financial relationships to disclose.